Abstract B29: A critical role of the SUMO pathway in KRAS-driven oncogenesis

The SUMOylation pathway modulates the activity of many cellular proteins and plays an important role in cellular stress protection. We identified the SUMO E2 ligase Ubc9 to be critical for KRAS-driven transformation in colorectal cancer cells. Ubc9 knockdown severely impairs clonogenic and anchorage-independent growth of KRAS mutant cells in vitro and attenuates tumor growth in xenograft models. Ubc9 mutant studies indicate that Ubc9 enzymatic activity is required for KRAS-driven transformation, thus Ubc9 inhibitor could be potentially useful in this setting. SILAC mass-spectrometry reveals that the SUMOylation of multiple proteins are elevated in KRAS mutant cells. Over-expression of some of these SUMO target proteins partially rescued transformation growth of KRAS mutant cells upon Ubc9 depletion. Our findings suggest a model where the SUMO pathway is required for relieving the oncogenic stress associated with KRAS transformation to maintain cell viability. Citation Format: Bing Yu, Steve Swatkoski, Alesia Holly, Liam Changwoo Lee, Valentin Giroux, Chih-Shia Lee, Joseph Carver, Chad Creighton, David K. Ann, William Douglas Figg, Marjan Gucek, Ji Luo. A critical role of the SUMO pathway in KRAS-driven oncogenesis. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B29. doi: 10.1158/1557-3125.RASONC14-B29